HemOnc vocabulary relationships

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The purpose of this page is to describe the existing relationships in the HemOnc ontology and to give examples. Most of the examples are based on adjuvant CapeOx for colon cancer, as described in the XELOXA study's primary publication (Schmoll et al. 2007, JCO). For an overview and information about how to obtain a copy of the ontology please go to this page. You can also follow this link to the Concepts page.

Internal relationships

The vast majority of the relationships in the HemOnc ontology are internal relationships, that is, relationships between two concepts that are native to the HemOnc vocabulary. Below are examples of common and less common internal relationships.

Common internal relationships and examples

These relationships occur at least 100 times in the most recent version of the ontology. This table is sortable; the default arrangement is alphabetical by relationship type. Note that in the actual relationship table, the HemOnc concept code is used, not the concept name as is shown here for clarity. For simplicity, relationships to regimen stubs or sig stubs are not shown, even if they occur more than 100 times.

Concept Type 1 Relationship Concept Type 2 Example 1 Relationship Example 2
Study Began enrollment in Year XELOXA Began enrollment in 2003
Regimen Can be followed by Regimen 7 plus 3i (induction) (HO:1095) Can be followed by HiDAC (consolidation) (HO:839)
Regimen Can be followed by Procedure FEC (neoadjuvant) Can be followed by Surgery
Regimen Can be preceded by Regimen HiDAC (consolidation) (HO:839) Can be preceded by 7 plus 3i (induction) (HO:1095)
Regimen Can be preceded by Procedure CapeOx (adjuvant) Can be preceded by Surgery
Study Ended enrollment in Year XELOXA Ended enrollment in 2004
Component Has accepted use Condition Capecitabine Has accepted use Colon cancer
Regimen Has accepted use Condition CapeOx Has accepted use Colon cancer
Regimen Has immunosuppressor Component Dexamethasone monotherapy Has immunosuppressor Dexamethasone
Regimen Has local therapy Component IT Cytarabine & Methotrexate Has local therapy Cytarabine
Regimen Has supportive med Component Carboplatin & Pemetrexed Has supportive med Dexamethasone
Regimen Has supportive med Component Class Bortezomib monotherapy Has supportive med Bisphosphonate
Regimen Has been compared to Regimen CapeOx Has been compared to FULV
Component Has brand name Brand Name Capecitabine Has brand name Xeloda
Regimen Has context Context CapeOx Has context Adjuvant therapy
Component Has FDA indication Condition Capecitabine Has FDA indication Colon cancer
Component Has FDA labeling Context Erlotinib Has FDA labeling Mutation-specific
Reference Has first author Author XELOXA::00 Has first author Schmoll_Hans Joachim
Reference Has middle author Author XELOXA::00 Has middle author Tabernero_Jose M
Reference Has last author Author XELOXA::00 Has last author Haller_Daniel G
Regimen Has min cycle length Duration CapeOx Has min cycle length 21 days
Regimen Has max cycle length Duration CapeOx Has max cycle length 21 days
Regimen Has min cycle num Numeric CapeOx Has min cycle num 1
Regimen Has max cycle num Numeric CapeOx Has max cycle num Indefinite
Regimen Has min duration Numeric CapeOx Has min duration 21 days
Regimen Has max duration Numeric CapeOx Has max duration Indefinite
Regimen Has modality Modality CapeOx Has modality Chemotherapy
Reference Has PMID PubMedURL XELOXA::00 Has PMID https://pubmed.ncbi.nlm.nih.gov/17194911
Reference Has URL ReferenceURL XELOXA::00 Has URL https://doi.org/10.1200/jco.2006.08.1075
Reference Has title ReferenceTitle XELOXA::00 Has title Phase III trial of capecitabine plus oxaliplatin as adjuvant therapy for stage III colon cancer: a planned safety analysis in 1,864 patients
Regimen Is current in Condition CapeOx Is current in Colon cancer
Regimen Is historical in Condition Edrecolomab monotherapy Is historical in Colon cancer
Component Was FDA approved Year Capecitabine Was FDA approved 1998
Reference Was published in Journal XELOXA::00 Was published in J Clin Oncol
Reference Was published year Year XELOXA::00 Was published year 2007
Regimen Has cycle Cycle Sigs CapeOx Has cycle 21-day cycle for 8 cycles
Study Has reference Reference XELOXA Has reference XELOXA::00
Study Has reported endpt Endpoint XELOXA Has reported endpt OS
Study Had experimental design Experimental design XELOXA Had experimental design In-class switch
Component Has route Route Capecitabine Has route PO
Study Has study group Study Group ECOG E3200 Has study group Eastern Cooperative Oncology Group
Study Has study type Study Class X-ACT Has study type FDA registration study
Component Has sig Sig Capecitabine Has sig 1000 mg/m^2 PO twice per day on days 1 to 14
Component Is a Component Class Capecitabine Is a Fluoropyrimidine
Component Class Is a Component Class Fluoropyrimidine Is a Pyrimidine analogue
Condition Is a Condition Colon cancer Is a Colorectal cancer
Regimen Is a Regimen Class CapeOx Is a Platinum doublet
Component May have route Route Dexamethasone May have route PO
Regimen Was studied in Study CapeOx Was studied in XELOXA
Context Was studied in Study Adjuvant therapy Was studied in XELOXA
Condition Was studied in Study Colon cancer Was studied in XELOXA

Uncommon internal relationships and examples

These relationships occur fewer than 100 times in the most recent version of the ontology. This list is currently incomplete. Note that some very uncommon internal relationships are likely due to logic errors and are actively being reviewed for correction.

Concept Type 1 Relationship Concept Type 2 Example 1 Relationship Example 2
Regimen Has antineoplastic Component CapeOx Has antineoplastic Capecitabine
Context Is a Context Adjuvant therapy Is a Post-definitive therapy
Regimen Has immunosuppressor Component Class Fludarabine & Melphalan Has immunosuppressor ATG (type not specified)
Regimen Has been compared to Procedure Cisplatin, Fluorouracil, RT Has been compared to Surgery
Regimen Has been compared to Regimen Class Ipilimuamb & Nivolumab Has been compared to Platinum doublet

External relationships

In order to increase general utility, the HemOnc ontology has relationships with several external vocabularies/terminologies. Note that external concepts are only present in the OMOP relationship table, and not in the OMOP concept table. These are defined by the vocabulary_id_2 field in the relationship table.

External terminologies that are currently supported

Healthcare Common Procedure Coding System (HCPCS)

HCPCS encodes billable drugs, the majority of which are administered. We update the HCPCS mappings for antineoplastic drugs regularly; we do not focus on mapping supportive medications at this time.

International Classification of Diseases for Oncology (ICD-O-3)

We map a small number of neoplastic conditions that do not have an NCIT code to ICD-O-3. We do not currently plan to map other conditions to ICD-O-3. Once ICD-O-4 is published, we will reconsider this decision.

National Cancer Institute thesaurus (NCIt)

NCI Thesaurus (NCIt) provides reference terminology for many NCI and other systems. It covers vocabulary for clinical care, translational and basic research, and public information and administrative activities. We currently map neoplastic conditions and regimens to NCIt concepts, when available. In the near future we plan to map procedures and potentially drugs.

OncoTree

OncoTree is a condition hierarchy maintained by Memorial Sloan Kettering Cancer Center. We currently map neoplastic conditions, when available.

RxNorm

RxNorm provides normalized names for clinical drugs and links its names to many of the drug vocabularies commonly used in pharmacy management and drug interaction software, including those of First Databank, Micromedex, and Gold Standard Drug Database. By providing links between these vocabularies, RxNorm can mediate messages between systems not using the same software and vocabulary. We currently map both antineoplastic and supportive drugs to RxNorm, and also have direct pointers from regimens to RxNorm drugs, as shown in the examples below.

RxNorm extension

The RxNorm extension is developed and maintained by OHDSI to capture drugs that are outside the normal scope of RxNorm. We currently map a small number of drugs to the RxNorm extension.

SEER Site Recode

The values of SEER site recode variables are based on the primary site and histology data fields submitted to SEER by the registries. The site recode variables define the major cancer site/histology groups that are commonly used in SEER's reporting of cancer incidence data and published statistics. The site recode variables are added to the SEER databases as a convenience for researchers. We currently map neoplastic conditions, when available.

Common external relationships and examples

These relationships occur at least 100 times in the most recent version of the ontology.

Concept Type 1 Relationship Concept Type 2 Example 1 Relationship Example 2
Regimen Has antineopl Rx RxNorm CUI CapeOx Has antineopl Rx 194000
Regimen Has immunosuppr Rx RxNorm CUI Dexamethasone monotherapy Has immunosuppr Rx 3264
Regimen Has local therap Rx RxNorm CUI CHOP-14 Has local therap Rx 3041
Regimen Has support med Rx RxNorm CUI Carboplatin & Pemetrexed Has support med Rx 3264
Component Maps to RxNorm CUI Capecitabine Maps to 194000
Component Maps to HCPCS code Capecitabine Maps to J8520; J8521
Condition Maps to NCIT CUI Colon cancer Maps to C4910
Condition Maps to OncoTree CUI Colon cancer Maps to COAD
Condition Maps to SEER Site Recode Colon cancer Maps to 21049

Uncommon external relationships and examples

These relationships occur less than 100 times in the most recent version of the ontology.

Concept Type 1 Relationship Concept Type 2 Example 1 Relationship Example 2
Condition Maps to ICD-O-3 code Acute promyelocytic leukemia Maps to 9866
Regimen Has antineopl Rx RxNorm Extension CUI Pixantrone monotherapy Has antineopl Rx OMOP997118
Component Maps to RxNorm Extension CUI Pixantrone Maps to OMOP997118

Further explanation of some relationships

Treatment modalities

In the HemOnc data model, treatment modalities are directed from regimen to drug (component), not vice versa. What this means is that the intent of the use of the drug defines the modality of the drug, not any intrinsic properties of the substance itself. For most drugs, the mechanism of action and the intent align in a 1:1 relationship, and there is no potential problem. However, there are several drugs, most notably the glucocorticoids and some drugs with cytotoxic chemotherapeutic properties, which can have different mechanisms of actions and different intents in different treatment contexts. Due to constraints of the OMOP data model, the names for these relationships ("Relationship ID") are by necessity abbreviated; longer forms are provided in the "Relationship expanded" column for additional guidance.

The following relationships are currently supported in the HemOnc model, as of July 2022:

Concept Type 1 Relationship ID Concept Type 2 Intent Example 1 Relationship expanded Example 2
Regimen Has AB-drug cjgt Component Systemic anticancer A-AVD Has antibody-drug conjugate therapy1 Brentuximab vedotin
Regimen Has antineoplastic Component Systemic anticancer R-CHOP Has antineoplastic therapy2 Doxorubicin
Regimen Has cytotoxic chemo Component Systemic anticancer R-CHOP Has cytotoxic chemotherapy Doxorubicin
Regimen Has endocrine tx Component Systemic anticancer Letrozole monotherapy Has endocrine tx Letrozole
Regimen Has immunosuppressor Component Non-cancer Alemtuzumab monotherapy Has immunosuppressive therapy3 Alemtuzumab
Regimen Has immunotherapy Component Systemic anticancer Ipilimumab & Nivolumab Has immunotherapy4 Nivolumab
Regimen Has local therapy Component Local anticancer Hyper-CVAD/MA Has local therapy5 Methotrexate6
Regimen Has pept-drug cjgt Component Systemic anticancer Melphalan flufenamide monotherapy Has peptibody-drug conjugate therapy1 Melphalan flufenamide
Regimen Has radioconjugate Component Systemic anticancer Ibritumomab tiuxetan protocol Has radioconjugate therapy1 Ibritumomab tiuxetan
Regimen Has radiotherapy Component Local anticancer Carboplatin & RT Has radiation therapy External beam radiotherapy
Regimen Has steroid tx Component Systemic anticancer R-CHOP Has systemic glucocorticoid therapy Prednisone
Regimen Has supportive med Component Supportive R-CHOP Has supportive medication Filgrastim
Regimen Has targeted tx Component Systemic anticancer R-CHOP Has targeted therapy Rituximab

1Some consider these drugs to be targeted therapy. While they do target a specific cell surface receptor, the antineoplastic action is through the drug or radiotherapy conjugate, which is usually a cytotoxic chemotherapy or radiotherapy.
2This is a more generic category, and we try to minimize its use.
3This category is used almost exclusively for non-malignant conditions, such as autoimmune cytopenia and graft-versus host disease.
4This category includes drugs that exert an indirect antineoplastic effect through activation of the immune system. Immune checkpoint inhibitors are the most commonly used drugs in this category.
5This category refers to drugs that are delivered to a local tissue, tumor, or space. This includes intrathecal administration of drugs that could have a systemic effect in other settings.
6In this regimen, methotrexate is used both as a systemic therapy and as an intrathecal therapy; the latter is the local therapy in this example.

Temporal relationships

Can be followed by

This directed relationship is phrased as an optional because there is always the possibility, even in a pre-defined protocol, that the patient will not go on to receive the second (or third, etc.) part of a treatment protocol.

Can be preceded by

This directed relationship is phrased as an optional because it is contextual; in many treatment contexts it is not necessary that the first treatment occurs before the second. In some treatment contexts the relationship is absolute, e.g., chemotherapy given in the adjuvant setting must by definition be preceded by a surgical procedure. This subtle distinction is not yet captured by the ontology.

FDA relationships

Has FDA indication

With very few exceptions, the FDA approves drugs, not regimens. Currently, all of these relationships in HemOnc are between components (drugs) and conditions.

Has FDA labeling

Most oncology labels issued by the FDA have specific contextual restrictions, which we are beginning to incorporate into HemOnc. Initially, we are focusing on labels that have a protein-expression or gene mutation requirement, i.e., a biomarker requirement. For example, the drug Erlotinib (Tarceva) is approved for first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 (L858R) substitution mutations.

Has route and May have route

Components with only one route of administration are related to that route using "Has route". Conversely, components with multiple routes of administration are related to those routes using "May have route".

Study-specific relationships

Has been compared to

This non-directional relationship is the pairwise comparison of two regimens in a randomized clinical trial. In the most common scenario one regimen is a control arm and the other is experimental arm, although this is not always the case.

Has reported endpt

For "negative" studies, which we define as those having p>0.10 regardless of the predeclared level of alpha, the reported endpoint is the primary endpoint. For "positive" studies, the reported endpoint is that which is the least surrogate with a p<0.10.

Has study type

Right now there is only one defined study class: FDA registration trials. We will plan to expand this in the near future to include details such as phase of study, whether a study was a cooperative group trial, etc.

Was replaced by

This is a special relationship type used to associate current and deprecated concepts. For example, "Imatinib monotherapy, high dose" has been replaced by "Imatinib monotherapy" and the replacement is captured by this relationship.